SMADS-Mediate Molecular Mechanisms in Sjögren's Syndrome

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-beta (TGF-beta), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-beta elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjogren's syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-beta/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-beta family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-beta in pSS that are dictated by orchestrations of SMADs, and describe TGF-beta/SMADs value as both disease markers and/or therapeutic target for pSS.